Osteoporotic femoral neck fracture and degenerative changes of knee and hip joints are common problems. For example, there are over 300,000 incidence of hip fracture reconstruction alone in the U.S., with a considerable degree of post-treatment disability (Campion E W, et al., J Gen Intern Med 2:78-82 (1987)), long-lasting independence (Guccione A. A, et al., Phys Ther 76:818-26 (1996)), post-surgical mortality causing from the use of bone cement (Bhandari M, et al., Int J Surg Investig 1:319-26 (1999)), high percentage of the revision surgery ranging 5%-40% (Espehaug B, et al., J Bone Joint Surg Br 84:832-8 (2002); Hudson J I, et al., Clin Orthop Relat Res: 59-66 (1998); Lu-Yao G L, et al., J Bone Joint Surg Am 76:15-25 (1994); Ravikumar and Marsh Injury 31:793-7 (2000); Tidermark J, et al., J Bone Joint Surg Br 85:380-8 (2003) and substantial reduction of quality of life (Tidermark J, et al., J Bone Joint Surg Br 85:380-8 (2003); Tidermark J, et al., J Orthop Trauma 17:S17-21 (2002)) Annual expenditures for the treatment of osteoporotic fractures are estimated at $13.8 billion (Ray N F, Chan J K, Thamer M, Melton L J, 3rd (1997). Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 12:24-35). The use of metallic implants as an anchor has become an essential measure for reconstructive treatment of such cases.
Bone regenerative therapy using growth factors has some success. For example, recombinant bone morphogenetic proteins (BMPs), as represented by BMP2 and BMP7, are the emerging therapeutic agents for bone regenerative therapy. In vitro, BMPs stimulate the differentiation of multopotential mesenchymal stem cells into osteoblastic linage. Osteoinductive capability of BMPS was demonstrated in ectopic sites in vivo. BMPs have key roles in development, growth and repair of bone. Limited FDA approval was recently obtained for the use of BMPs in selected applications, such as spine fusions and non-unions. Clinically, BMPs seem to be effective only when used in high dose (Govender S, et al., J Bone Joint Surg Am 84-A: 2123-2134 (2002)). However, although the proved overall effects of BMPs on promoting fracture healing and reducing infection rate, inconsistency is found in its effectiveness: the significant percentage of patients are not suseptable for the BMPs (Govender et al., 2002, supra). Inherently, BMPs involves concerns in protein degradation, mode of delivery and high cost.
Severe adverse effects of bone cement on systemic conditions have been reported. Bone cement implantation syndrome (BCIS) is characterized by hypotension, hypoxaemia, cardiac arrhythmias, cardiac arrest or any combination of these, leading to an immediate death in 0.6-1% of the recipients ((Bhandari M, et al., Int J Surg Investig 1:319-26 (1999); Lamade W R, et al., Arch Orthop Trauma Surg 114:335-9 (1995)).
Therefore, there is a need for osteogenic enhancer composition for bone and/or cartilage repair.
The composition and methods of making the polymer and implantable materials disclosed herein address the above described problems.